The objectives of these investigations are the evaluation of specific aspects of pathogenetic and host defense mechanisms of importance in infections caused by Gram-negative bacilli. Genetically determined resistance to LPS, which can be assessed by B lymphocyte and macrophage reactivity to LPS, has been demonstrated in mice. Investigations will be undertaken to evaluate whether variations in lymphocyte or macrophage reactivity to LPS can be identified in man and whether cellular reactivity to LPS can be correlated with susceptibility to the complications of Gram-negative bacteremia and toxicity after immunization with Gram-negative bacilli. Other investigations will continue evaluations of the significance of the serum bactericidal reaction in clinical infections and the role of antibody to individual antigenic components of Gram-negative bacilli in opsonic, bactericidal, and protective activity. Previously initiated studies of the isolation, purification, and chemical characterization of Common Enterobacterial Antigen from both "immunogenic" and "non-immunogenic" Enterobacteriaceae will be continued and extended.